rs762024937

Variant names:

• chr5-176597515-C-A
• rs762024937
• NM_052899.3:c.2320G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-176597515-C-A
• chr5-176597515-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_052899.3(GPRIN1):​c.2320G>T​(p.Glu774*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000755 in 1,324,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: GPRIN1 NM_052899.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209
• Publications: 0 publications found

Genes affected

GPRIN1 (HGNC:24835): (G protein regulated inducer of neurite outgrowth 1) Predicted to enable phosphoprotein binding activity. Predicted to be involved in neuron projection development. Predicted to be located in growth cone. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRIN1	NM_052899.3	c.2320G>T	p.Glu774*	stop_gained	Exon 2 of 2	ENST00000303991.5	NP_443131.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRIN1	ENST00000303991.5	c.2320G>T	p.Glu774*	stop_gained	Exon 2 of 2	1	NM_052899.3	ENSP00000305839.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.55e-7 AC: 1 AN: 1324664 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 648330

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28866

American (AMR) AF: 0.00 AC: 0 AN: 28428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22850

East Asian (EAS) AF: 0.00 AC: 0 AN: 33170

South Asian (SAS) AF: 0.00 AC: 0 AN: 74246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4808

European-Non Finnish (NFE) AF: 9.57e-7 AC: 1 AN: 1044708

Other (OTH) AF: 0.00 AC: 0 AN: 54746

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	27
DANN	Benign	0.94
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.11	N
PhyloP100		0.21
Vest4		0.48
GERP RS		-6.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=68/132	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs762024937; hg19: chr5-176024516;